Effects of Phthalate Esters on Human Myometrial and Fibroid Cells: Cell Culture and NOD-SCID Mouse Data

Autor: Hyun-Jin Kim, Do Young Kim, Sung-Hoon Kim, Kang-Hyun Kim, Seung-Ho Heo, Hee Dong Chae, Young Sang Oh, Sa Ra Lee
Rok vydání: 2020
Předmět:
Vascular Endothelial Growth Factor A
0301 basic medicine
Angiogenesis
Apoptosis
Mice
SCID
Nod
Collagen Type I
Andrology
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Mice
Inbred NOD
Diethylhexyl Phthalate
Tumor Cells
Cultured
medicine
Animals
Humans
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
Protein kinase B
Cell Proliferation
Severe combined immunodeficiency
030219 obstetrics & reproductive medicine
Leiomyoma
Neovascularization
Pathologic
business.industry
Myometrium
Obstetrics and Gynecology
Esters
medicine.disease
female genital diseases and pregnancy complications
Vascular endothelial growth factor
030104 developmental biology
chemistry
Uterine Neoplasms
Disease Progression
Female
business
Proto-Oncogene Proteins c-akt
Signal Transduction
Zdroj: Reproductive Sciences. 28:479-487
ISSN: 1933-7205
1933-7191
DOI: 10.1007/s43032-020-00341-0
Popis: Evidence is growing that phthalate esters play an important role in the pathogenesis of estrogen-dependent gynecologic diseases, especially uterine fibroids. We aimed to investigate whether in vitro treatment with di-(2-ethylhexyl)-phthalate (DEHP) affects angiogenesis, proliferation, and apoptosis in uterine fibroids. To ascertain this, we evaluated vascular endothelial growth factor (VEGF) expression and AKT/ERT phosphorylation and compared the fibroid volume between nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice fed with and without DEHP. VEGF expression was measured using enzyme-linked immunosorbent assay, and AKT/ERK phosphorylation was analyzed by western blot analysis in human myometrial and fibroid cells. The volume of the fibroid tissues implanted to NOD/SCID mice was measured, and the expression of collagen type I protein, Ki-67, proliferating cell nuclear antigen, and B cell lymphoma 2 were analyzed using immunohistochemistry. We could see significant increases in VEGF expression and AKT phosphorylation in human myometrial and fibroid cells treated with DEHP. The volume of the fibroid tissues was significantly increased in NOD/SCID mice fed with DEHP, which was accompanied by increased expression of collagen type I and AKT phosphorylation. Taken together, these results suggest that exposure to phthalate esters may influence uterine fibroid pathogenesis by increasing VEGF and collagen expression and upregulating AKT phosphorylation.
Databáze: OpenAIRE
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